New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds.
Bioorg Med Chem Lett
; 26(16): 3896-904, 2016 08 15.
Article
en En
| MEDLINE
| ID: mdl-27423478
ABSTRACT
Purinergic P2X3 receptors are trimeric ligand-gated ion channels whose antagonism is an appealing yet challenging and not fully validated drug development idea. With the aim of identification of an orally active, potent human P2X3 receptor antagonist compound that can penetrate the central nervous system, the compound collection of Gedeon Richter was screened. A hit series of tricyclic compounds was subjected to a rapid, two-step optimization process focusing on increasing potency, improving metabolic stability and CNS penetrability. Attempts resulted in compound 65, a potential tool compound for testing P2X3 inhibitory effects in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mesilatos
/
Receptores Purinérgicos P2X3
/
Antagonistas del Receptor Purinérgico P2X
/
Compuestos Heterocíclicos
/
Compuestos Heterocíclicos con 3 Anillos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Hungria